This proposal outlines the salient features of the design and development of synthetic methods and reagents for seven-membered ring synthesis and their application to the synthesis of the potent tumor promoters and inhibitors represented by phorbol derivatives, mezerein, and ingenol. The major objectives of this investigation include the development of approaches to tigliane, daphnane, and igenane synthesis based on the divinylcyclopropane rearrangement, an intramolecular Diels-Alder reaction for bicyclic synthesis, an intramolecular photocycloaddition for bicyclic synthesis, and an intramolecular 6Pi + 4Pi cycloaddition. A Diels-Alder/ring expansion sequence for seven-membered ring synthesis will also be examined in connection with a synthesis of quadrone. Degradation studies designed to facilitate realization of the synthesis objectives are also planned along with a collaborative effort to evaluate the biological activity of the intermediates and targets produced as part of this research.